วันพฤหัสบดีที่ 26 กุมภาพันธ์ พ.ศ. 2569

Approach to Unexpected Thrombocytopenia

Approach to Unexpected Thrombocytopenia

1. INTRODUCTION

Thrombocytopenia คือ platelet count <150,000/µL ในผู้ใหญ่ และมี clinical spectrum ตั้งแต่ incidental finding life-threatening bleeding หรือ thrombosis (เช่น ITP, HIT, TTP, DIC)

แนวทางประเมินต้องตอบ 4 คำถามหลัก:

1.       Thrombocytopenia จริงหรือไม่ (artifact?)

2.       เป็น acute หรือ chronic?

3.       isolated หรือมี cytopenia อื่นร่วม?

4.       มีภาวะฉุกเฉินที่ต้องรักษาทันทีหรือไม่ (TTP, HIT, DIC ฯลฯ)

ใช้ได้ทั้งใน primary care, ER, ICU และ hematology consult


2. DEFINITIONS & CLINICAL SIGNIFICANCE

2.1 Severity classification

ระดับ

Platelet count

Mild

100–149 x10/L

Moderate

50–99 x10/L

Severe

<50 x10/L

Very severe (clinical)

<20–30 x10/L

ใน ITP มักใช้ <30,000/µL เป็น severe


2.2 Platelet count interpretation (clinical pearl)

  • Platelet count มี narrow range ต่อ “แต่ละบุคคล”
  • drop จาก 400k 200k = clinically significant แม้ยัง >150k
  • ต้องดู trend + baseline เสมอ

3. BLEEDING RISK: WHEN TO WORRY

3.1 Platelet count vs bleeding (important concept)

Correlation “weak” bleeding risk ขึ้นกับ:

  • Platelet function
  • Coagulopathy
  • Underlying disease
  • Anticoagulant/antiplatelet drugs

3.2 Clinical predictors of bleeding (สำคัญกว่า platelet number)

  • Prior bleeding history
  • Wet purpura (oral/mucosal)
  • Hematuria
  • Hematologic malignancy

3.3 Practical bleeding thresholds (clinical guide)

Platelet

Clinical risk

>50k

surgery usually safe

>100k

neurosurgery/major surgery

<20k

spontaneous bleeding

<10k

high risk life-threatening bleeding

Note:
ITP bleeding risk < aplastic anemia at same platelet (young functional platelets)


4. WHEN TO WORRY ABOUT THROMBOSIS (CRITICAL)

Thrombocytopenia protection from thrombosis

ต้องคิดถึง:

  • HIT (heparin 5–10 วัน)
  • PITT/VITT (anti-PF4 syndromes)
  • APS
  • DIC
  • TTP/HUS (TMA)
  • PNH
  • ITP + thrombosis (AF, VTE)

5. MAJOR PATHOPHYSIOLOGIC MECHANISMS (High-yield framework)

5.1 Decreased production (bone marrow failure)

สาเหตุสำคัญ:

  • Aplastic anemia
  • MDS / leukemia
  • Bone marrow infiltration (cancer)
  • B12 / Folate / Copper deficiency
  • Severe infection
  • Liver disease (TPO)
  • PNH (BM failure component)

Clue:

  • Pancytopenia
  • Anemia + thrombocytopenia
  • Abnormal smear

5.2 Increased destruction / clearance

Immune-mediated

  • Primary ITP (common)
  • Secondary ITP (SLE, HIV, HCV)
  • Drug-induced immune thrombocytopenia
  • Post-transfusion purpura

Lab pattern:

  • Normal fibrinogen
  • Normal D-dimer

5.3 Consumptive thrombocytopenia (thrombotic/critical)

Life-threatening group:

  • DIC
  • HIT
  • TTP/HUS (TMA)
  • PITT/VITT

Lab clue:

  • D-dimer
  • fibrinogen (DIC)
  • Schistocytes (TMA)

5.4 Redistribution / sequestration

  • Splenomegaly
  • Cirrhosis / portal hypertension
  • MASLD (metabolic dysfunction-associated steatotic liver disease = NAFLD)
    Typical platelet: 60–100k (mild–moderate)

5.5 Dilutional

  • Massive transfusion
  • Fluid resuscitation
  • Postoperative (day 2–3)

6. EMERGENCY THROMBOCYTOPENIA (DO NOT MISS)

ต้อง consult hematologist ด่วนถ้าสงสัย:

  • TTP / HUS / TMA (thrombotic microangiopathy)
  • HIT / PITT
  • Acute DIC
  • Acute leukemia
  • Aplastic anemia
  • HLH
  • Severe bleeding + platelet <50k
  • Pregnancy + severe thrombocytopenia

7. CLINICAL CONTEXT-BASED DIFFERENTIAL

7.1 ICU / critically ill (common causes)

  • Sepsis (most common)
  • DIC
  • Drug-induced
  • Liver disease
  • Massive transfusion
  • Multicausal

7.2 Postoperative thrombocytopenia

  • Nadir: 48–72 hr
  • Mechanism: dilution + consumption
  • CPB: drop up to 50%

7.3 Infection-related thrombocytopenia

Viral

  • EBV, hepatitis C, HIV
  • COVID-19
  • Dengue, SFTS (severe fever with thrombocytopenia syndrome) (SE Asia relevance clinically)

Bacterial/sepsis

  • DIC
  • marrow suppression

Parasite

  • Malaria, babesiosis

8. APPROACH TO EVALUATION (Step-by-Step Clinical Algorithm)

STEP 1: Confirm it is REAL

  • Repeat CBC
  • Peripheral smear review
  • Rule out pseudothrombocytopenia (EDTA clumping)

Key cause:

  • EDTA-dependent platelet clumping (~0.1%)

STEP 2: Assess severity & urgency

  • Bleeding?
  • Platelet <50k?
  • Thrombosis?
  • Acute illness?

STEP 3: Focused history (high-yield checklist)

Essential history:

  • Previous platelet counts (trend)
  • Drug exposure (last 2 weeks!)
  • Heparin exposure (flush included)
  • Transfusion history
  • Infection/travel (malaria, dengue)
  • Alcohol use
  • Autoimmune disease
  • Diet (B12, folate, zinc excess)
  • Family history (inherited thrombocytopenia)

STEP 4: Physical examination clues

Finding

Suggests

Petechiae/purpura

platelet disorder

Wet purpura

severe bleeding risk

Splenomegaly

hypersplenism/liver disease

Lymphadenopathy

lymphoma/infection

Neurologic signs

TTP/TMA

Thrombosis

HIT, APS, PNH


9. LABORATORY WORKUP (CORE PANEL)

9.1 Mandatory baseline tests

  • CBC + smear (critical)
  • LFT + metabolic panel
  • PT/aPTT
  • HIV testing
  • HCV testing

9.2 Peripheral smear key clues

Finding

Diagnosis clue

Schistocytes

TMA / DIC

Giant platelets

inherited disorder / ITP

Blasts

leukemia

Hypersegmented neutrophils

B12/folate deficiency

Leukoerythroblastic picture

marrow infiltration


9.3 Targeted tests (based on suspicion)

  • D-dimer, fibrinogen DIC
  • LDH, Cr TMA
  • Anti-PF4 Ab HIT
  • ANA / APL Ab autoimmune
  • Cultures sepsis
  • Bone marrow biopsy unclear etiology / pancytopenia

10. COMMON CLINICAL SCENARIOS

10.1 Isolated thrombocytopenia + normal CBC

Most likely:

  • ITP
  • Drug-induced thrombocytopenia
  • Viral infection
  • Early liver disease

10.2 Pancytopenia

Think:

  • Aplastic anemia
  • MDS
  • Leukemia
  • Bone marrow infiltration
  • Severe infection
  • Nutritional deficiency

10.3 Mild incidental thrombocytopenia (100–149k)

Common causes:

  • Normal variation
  • Early ITP
  • Occult liver disease
  • HIV/HCV
  • MDS (long-term risk)

11. DIAGNOSIS OF EXCLUSION (VERY HIGH-YIELD)

11.1 Drug-induced thrombocytopenia

  • Onset: 1–2 weeks (new drug)
  • Hours if prior exposure
  • Recovery: 5–7 days after stopping drug
    Common drugs:
  • Antibiotics (vancomycin, rifampin, beta-lactams)
  • Antiepileptics (phenytoin, carbamazepine)
  • Heparin (special: HIT)

11.2 Immune thrombocytopenia (ITP)

Diagnosis when:

  • Isolated thrombocytopenia
  • Normal smear
  • No systemic illness
  • Negative secondary causes

Bone marrow not routinely required


12. GENERAL MANAGEMENT PRINCIPLES (Practical Clinical)

12.1 Treat underlying cause (core principle)


12.2 Platelet transfusion indications

  • Active life-threatening bleeding
  • Platelet <10,000 (prophylaxis)
  • Urgent invasive procedure
  • Not routinely for ITP (unless bleeding)

12.3 Medications & precautions

Avoid:

  • NSAIDs
  • Aspirin
  • Ginkgo
  • Antiplatelets (if not essential)

12.4 Anticoagulation in thrombocytopenia

Key concept:

Thrombocytopenia does NOT protect from thrombosis

  • 50k: anticoagulation usually acceptable if indicated
  • <50k: individualized decision

12.5 Activity restriction

  • <50k: avoid high-impact sports
  • Routine daily activity: usually safe

13. WHEN TO REFER HEMATOLOGY (Strong Indications)

  • New unexplained thrombocytopenia
  • Platelet <50,000
  • Suspected TTP/HIT/DIC
  • Pancytopenia
  • Abnormal smear (blasts, schistocytes)
  • Need urgent procedure
  • Pregnancy + thrombocytopenia

14. KEY CLINICAL PEARLS (Exam + Practice)

  • Always rule out pseudothrombocytopenia first
  • Trend > single platelet value
  • Isolated thrombocytopenia = ITP or drug until proven otherwise
  • Schistocytes + thrombocytopenia = TMA emergency
  • Heparin exposure + platelet drop >50% = think HIT
  • Mild thrombocytopenia + splenomegaly = hypersplenism
  • ICU thrombocytopenia = sepsis most common
  • Platelet count alone poorly predicts bleeding

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